Voltage-dependent calcium channel subunit alpha-2/delta-3

CACNA2D3 encodes the alpha-2/delta-3 subunit of voltage-dependent calcium channels (UniProt: Q8IZS8). This regulatory subunit modulates calcium current density and the activation/inactivation kinetics of P/Q-type, N-type, and L-type calcium channels, functioning as an auxiliary component that fine-tunes channel behavior without directly forming the ion-conducting pore.

The protein is expressed across tissues requiring calcium-dependent signaling and is particularly relevant in neurons where voltage-dependent calcium channels govern neurotransmitter release and synaptic plasticity. CACNA2D3 associates with multiple calcium channel isoforms encoded by genes including CACNA1A, CACNA1B, CACNA1C, and CACNA1D, but not T-type channels, indicating selective regulatory partnerships within the calcium channel superfamily.

CACNA2D3 is curated as a SFARI Category 2 gene (SFARI Cat 2), reflecting evidence implicating this locus in autism spectrum disorder risk. This classification suggests a probable role in ASD etiology, though the specific molecular mechanisms linking calcium channel dysregulation to autism phenotypes require further investigation.